RESUMO
Objective:To investigate the effect of sodium octanoate on renal-intestinal ischemia- reperfusion injury (IRI) after resuscitation from traumatic cardiac arrest in pigs.Methods:Twenty-two miniature piglets with a body weight of (37.6±2.5)kg were divided into three groups according to the random-number table method: normal group ( n=7), IRI group ( n=7) and IRI-treated group ( n=8). A renal-intestinal IRI model of the pig was established by allowing femoral artery to bleed through blood pump at a rate of 2 ml·kg -1·min -1 until cardiac arrest, followed by whole blood transfusion through the femoral vein at a rate of 5 ml·kg -1·min -1 after observation for 6 minutes, and 50% of total blood loss was reinfused before resuscitation. Both the IRI group and IRI-treated group were with IRI model, while normal group was just monitored without induction of IRI. Besides, IRI-treated group was injected intravenously with sodium octanoate (30 mg/kg) for 1 hour at 5 minutes after restoration of spontaneous circulation (ROSC). (1) The rate of resuscitation success, survival rate at 4, 24 hours after resuscitation, blood loss when reaching cardiac arrest criteria and resuscitation time when reaching the ROSC criteria were compared in the three groups. (2) Levels of serum creatinine (SCr), urea nitrogen (BUN), intestinal fatty acid binding protein (iFABP) and diamine oxidase (DAO) were measured before resuscitation and at 1, 2, 4, 24 hours after resuscitation. (3) The animals were sacrificed at 24 hours post-resuscitation to harvest renal and intestinal tissues rapidly. TUNEL test was applied for the cellular apoptosis index. Prussian blue was used to detect the rate of iron deposition. Western blot analysis was used to measure levels of glutathione peroxidase 4 (GPX4) and acyl-CoA synthetase long-chain family member4 (ACSL4). Results:In three groups, all pigs survived. There was no significant difference in blood loss or resuscitation time between IRI group and IRI-treated group (all P>0.05). There was no significant difference in levels of SCr, BUN, iFABP or DAO before resuscitation and at 1, 2, 4, 24 hours after resuscitation in normal group (all P>0.05). But their levels were gradually increased at 1, 2, 4, 24 hours after resuscitation from that before resuscitation in IRI group and IRI-treated group (all P<0.01). Among three groups, levels of SCr, BUN, iFABP and DAO had no significant difference before resuscitation (all P>0.05), but showed obvious increase in IRI group and the IRI-treated group at 1, 2, 4, 24 hours after resuscitation compared with normal group, especially in IRI group (all P<0.01). In normal group, IRI group and IRI-treated group after 24 hours for resuscitation, the cellular apoptosis index of renal tissues was (2.3±0.8)%, (44.0±5.4)% and (13.8±4.3)%; the cellular apoptosis index of intestinal tissues was (2.6±0.9)%, (61.3±10.4)% and (20.8±3.7)%; the rate of iron deposition of renal tissues was (0.6±0.1)%, (3.9±1.0)% and (1.7±0.3)%; the rate of iron deposition of intestinal tissues was (0.8±0.1)%, (4.9±0.9)% and (2.1±0.5)% (all P<0.01). The cellular apoptosis index and rate of iron deposition of both renal and intestinal tissues were the highest in IRI group. The renal-intestinal expression of GPX4 in IRI group and IRI-treated group was lower than that in normal group at 24 hours after resuscitation (all P<0.05), with the lowest in IRI group. The renal-intestinal expression of ACSL4 in IRI group and IRI-treated group was higher than that in normal group at 24 hours after resuscitation (all P< 0.01), with the highest in IRI group. Conclusion:Sodium octanoate can reduce renal-intestinal IRI after resuscitation from traumatic cardiac arrest in pigs, the mechanism for which is probably due to that sodium octanoate can inhibit cellular apoptosis and reduce ferroptosis by regulating the expression levels of GPX4 and ACSL4.